[Genes and enzymes involved in the metabolism of carcinogens]

Most chemical carcinogens are not by themselves reactive. They are in fact procarcinogens and, before becoming toxic, they must undergo some metabolic transformations, directed by enzymatic systems under genetic control. Because of this system of defence, xenobiotics undergo in vivo a more or less sophisticated metabolic process that usually involved at least two phases: after activation phase (or "functionalization"), then a conjugation phase that allows elimination of the processed molecule. The initial step is in most cases on oxidation by P450 cytochroms. The conjugation step may involve a molecule of sulfate (sulfotransferase), of glucuronate (glucuronyltransferase) or of glutathione (glutathione-S-transferase). In man, large interindividual variations in the the expression in these enzymes have been demonstrated, probably depending on a genetic polymorphism. They are responsible for variations in individual susceptibility to carcinogens.